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General Information
Name
obesity, susceptibility to (postulated), THADA-related
FlyBase ID
FBhh0000677
Disease Ontology Term
Parent Disease
OMIM
Overview

In GWAS studies, the human THADA gene has been associated with cold adaptation and type 2 diabetes. It is also in the region of a strongly selected SNP in modern human genomes compared to the Neanderthal genome (Green et al., 2010; pubmed:20448178). There is a single orthologous gene in Drosophila, also designated THADA, for which amorphic alleles created by targeted recombination and RNAi targeting constructs have been generated. Recent experiments characterizing the Drosophila ortholog show that the fly protein localizes primarily to the ER and that it modulates, via calcium signaling, energy storage and thermogenesis balance (FBrf0235198).

A UAS construct of the wild-type human Hsap\THADA gene has been introduced into flies. Heterologous rescue (functional complementation) has been demonstrated: the obesity phenotype of adults homozygous for an amorphic Dmel\THADA allele is rescued by induced expression of the human gene.

Animals that homozygous for amorphic alleles of Dmel\THADA are obese, hyperphagic, have reduced energy production, and are sensitive to the cold. A single physical interaction for Dmel\THADA has been described; see below and in the THADA gene report.

[updated Dec. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: obesity, susceptibility to (fly models overview)
Symptoms and phenotype

Obesity is an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. Obesity is associated with increased risk of illness, disability, and death. (http://medical-dictionary.thefreedictionary.com/obesity).

The development of obesity is recognized as having both genetic and environmental components (https://www.sciencelearn.org.nz/resources/203-obesity-genetic-or-environmental).

Specific Disease Summary: obesity, susceptibility to (postulated), THADA-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics

THADA is associated with Type 2 diabetes in multiple GWAS studies (see GWAS Catalog, below in 'External links').

Cellular phenotype and pathology
Molecular information

Recent experiments characterizing the Drosophila ortholog show that THADA localizes primarily to the ER and that it modulates, via calcium signaling, energy storage and thermogenesis balance (FBrf0235198).

External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    THADA (THADA) encodes a metabolic regulator that controls the balance between fat storage and heat production. It physically interacts with the ER calcium pump encoded by SERCA and regulates its activity to control metabolism. [Date last reviewed: 2018-10-04]
    Molecular function (GO)
    Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate-scoring ortholog of human THADA (1 Drosophila to 1 human); Dmel\THADA shares 22% identity and 38% similarity with the human gene.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (1 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
        Models Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Interaction
        References
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        amorphic allele - molecular evidence
        ends-out gene targeting
        amorphic allele - molecular evidence
        ends-out gene targeting
        References (5)